Establishment of tandem mass spectrometric fingerprint of novel antineoplastic curcumin analogues using electrospray ionization

Abstract

This is the pre-peer reviewed version of the following article: Awad, H., Das, U., Dimmock, J., and El-Aneed, A. (2015), Establishment of tandem mass spectrometric fingerprint of novel antineoplastic curcumin analogues using electrospray ionization. Rapid Commun. Mass Spectrom., 29, 1307-1316, which has been published in final form at doi: 10.1002/rcm.7222. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. ABSTRACT RATIONALECurcumin analogues are antineoplastic agents, designed based on the structure of the spice turmeric with structural modifications aiming at enhancing potency. The goal is to identify the common tandem mass spectrometric (MS/MS) behavior of 13 novel curcumin analogues. Such knowledge is critical for their biological assessment, including metabolite identification and pharmacokinetic evaluation. METHODSBoth detection of the protonated molecules [M+H] + of the synthesized compounds and determination of their exact molecular masses were achieved with a hybrid quadrupole orthogonal time-of-flight mass spectrometer (QqTOF-MS). Low-energy collision induced dissociation (CID)-MS/MS analysis was performed using a triple quadrupole linear ion trap mass spectrometer (QqLIT-MS). Both instruments were equipped with an electrospray ionization (ESI) source. MS 3 and neutral loss experiments were performed using the QqLIT-MS to confirm the genesis of the observed product ions. RESULTSAbundant [M+H] + molecules were formed using the QqTOF-MS hybrid instrument with mass accuracies below 6 ppm. CID-MS/MS dissociation studies were centered on the piperidone ring of curcumin analogues;twelve common product ions have been identified from the fission of the various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions, stabilized via resonance. The variety of the side chain substituents at the nitrogen atom resulted in side chain-specific product ions. CONCLUSIONSThe ESI-CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of all tested compounds, which gave diagnostic product ions identified for each molecule. The established MS/MS behavior will be applied to determine metabolic by-products of curcumin analogues as well as to develop targeted identification/quantification methods within biological extracts.

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